Post on 18-Jan-2022
دانشگاه علوم پزشکی گیلان
Dosing Consideration in
Pediatrics
Dr. Maryam Shahrokhi
عضو هیئت علمی دانشگاه علوم پزشکی گیلان
متخصص داروسازی بالینی
Solid Dosage Forms
Advantage of Pill Splitting:
Different tablet strengths often cost about the same. Patients who cannot afford their medications have received a higher strength tablet with directions to take ½ tablet (or even ¼ tablet) per dose
Some health insurers have denied payment of prescriptions for the lower strength of certain drugs, thus requiring patients to receive the higher strength tablet and split it in half for each dose
Some healthcare organizations have not purchased all commercially available strengths of oral medications. Thus, some of the drugs may require tablet splitting for patient-specific doses in the inpatient setting.
Patients may not be able to swallow whole tablets
Medication factors.
Enteric-coated/extended-release tablets
Very small tablets
Asymmetrical tablets
Capsules
Teratogenic medications (e.g., bosentan).
Factors That Affect Pill Splitting
Hard outer coated tablet - Hard outer coating will make it tough to split and it will also alter the absorption in our body.
Extended release pill - This tablet will be formulated such that it will release the medicine slowly in our body throughout the day and this property will get affected because of splitting.
Small pills, which cannot get split.
Capsules have to be taken as a whole always as it contains gel or powder in it.
One should not split a vial. If medicine is exposed to oxygen it may degrade the content and affect the drugs.
tablet splitting is preferable to dispersing or crushing tablets and giving a proportion of the tablet
to split tablets, use a tablet splitter, which should be cleaned and replaced following manufacturer and local specifications
tablets should be split along the scoreline
if the tablet is not scored, consult a pharmacist prior to splitting
tablets should not be split into less than quarter segments, unless according to manufacturer specifications
tablets should be assessed visually to ensure segments appear equal in size
storing tablet segments should be in accordance with local policies
The tablet should split consistently into equal parts using
either the fingers or a tablet splitting device. Use of a
device is preferred.
The medication should be of a pharmacologic and
pharmacokinetic nature such that small variations in daily
dose are unlikely to adversely affect patient response to
therapy. For example, Narrow Therapeutic Index
medications should not be included in a tablet splitting
program.
The drug selected should be supported by clinical data
demonstrating desired clinical
outcomes, data demonstrating the bioequivalence of split
tablets, or meet weight variation specifications.
•The health system’s Pharmacy and Therapeutics Committee
or equivalent body should approve the tablets that meet the
selection criteria for tablet splitting.
Physicians, pharmacists and patients or their caregivers should
be encouraged to report any problems with tablet‐splitting
options.
A physician should be allowed to designate that a specific
patient is not an appropriate candidate for tablet splitting.
A patient or caregiver should have the right to request an
exception to tablet splitting with appropriate justification.
Tablets That May Require Special
Consideration
Tablets with special coatings to protect the drug from
moisture.
Tablets with enteric coatings that prevent them from
dissolving in the stomach.
Time‐release and extended release tablets and capsules, if
the coating is an integral part of the release mechanism.
Tablets that cannot be consistently split into equal parts,
adversely affecting patient response to therapy.
Tablets containing two medications, in which the desired
dose would be obtained for only one of the two
medications
Drugs Suitable for Split:
FDA (Food and Drug Administration) has issued a list of
drugs which can be split and also the warnings and risks.
Most of the drugs which are prescribed for the treatment
of high cholesterol (statins), high blood pressure
and depression will be suitable for split.
Medicines suitable for safe split are as follows: (a)
Atorvastatin, (b) Lovastatin, (c) Rosuvastatin, (d)
Pravastatin, (e) Simvastatin, (f) Amlodipine, (g) Atenolol, (h)
Doxazosin, (i) Lisinopril, (j) Metoprolol, (k) Quinapril, (l)
Citalopram, (m) Clonazepam, (n) Olanzapine, (o)
Paroxetine, (p) Sertraline, (q) Finasteride, (r) Sildenafil, (s)
Tadalafil, (t) Vardenafil, (u) Levothyroxine, (v) Metformin
Drugs Not Suitable for split
Medicines not suitable for split are Oxycodone (pain),
Omeprazole (heart burn), Cetirizine (allergy), anti-seizure
medications, birth control pills, blood thinners such as
Warfarin and Coumadin and chemotherapy drugs.
Don't use scissors or kitchen knives to cut tablets—this causes uneven splitting and crumbling, which changes the correct dose.
Don't split extended-release or time-release medication.
Don’t split very small or unevenly shaped tablets.
Don't split the entire vial of tablets at one time—air degrades the exposed drug.
Do split your tablets only as you need them to maintain potency.
Do use a commercially available tablet-cutting device.
Do talk to your pharmacist if you have any physical limitations (such as arthritis) that would keep you from splitting tablets accurately or for any other concerns about tablet-splitting.
Liquid Dosage Forms
Storage & Stability
Measurement
تجویز داروهای وریدی
مصرف داروهای وریدی
داروهایی که از طریق وریدی مصرف می شوند، قدرت و سرعت اثر
بالاتری در مقایسه با فرم خوراکی دارند
یکی از نگرانیهای مهم در مصرف فراورده های وریدی، نحوه آماده
و نحوه ناسازگاری این فراورده ها با حاملها و داروهای دیگر, سازی
تزریق است
Advantages & Disadvantages of I.V.
medications
Advantages
Provide direct access to the circulatory system
A route for drugs that do not irritate the gastric mucosa
A route for instant drug action
A route for delivering high drug concentrations
Instant drug termination if sensitivity or an adverse reaction occurs
Route of administration in patients in whom use of the GI tract is
limited
Advantages & Disadvantages of
I. V. administration cont
Disadvantages
Drug interaction because of incompatibilities
Adsorption of the drug being impaired because of leaching into
the I.V. container or administration set
Errors in compounding of medication
Speed shock
Extravasation of a vesicant drug
Chemical phlebitis
Common error in Administering Medications
Lack of knowledge about drugs
Errors in drug identity checking
Mistakes in calculations
Improper use of pumps and controllers
Drug incompatibilities
Three broad categories
Physical: occur when one drug is mixed with other drugs or solutions
to produce a product that is unsafe for administration
Chemical: a reaction of a drug with other drugs or solutions, which
results in alterations of the integrity and potency of the active ingredient
Therapeutic: an undesirable effect occurring in a patient as a result of
two or more drugs being given concurrently
I. V. Medication delivery
IV medication can be delivered by
Continuous infusion
Intermittent infusion
IV push
مصرف داروهای وریدی
زمانی که داروها به حاملی اضافه می شوند، یا چند دارو همزمان در یک
:حامل تجویز می شوند
مونو گراف دارو باید چک شود تا داروها با هم ناسازگار نباشند
داروها نباید به فراورده های زیر اضافه شوند:
مانیتول
بیکربنات سدیم
فراورده های خونی
تغذیه وریدی
امولسیونهای دارویی نظیر پروپوفول
مصرف داروهای وریدی
کهایی فراورده های وریدی که نیاز به آماده سازی دارند نظیر آنتی بیوتی
اده که به صورت پودر فرموله می شوند، بایستی بلافاصله پس از آم
سازی مصرف شوند
و تاخیر در مصرف ممکن است منجر به رشد میکروبی، تخریب و تجزیه دار
گردد
دستورالعمل آماده سازی داروهای وریدی
نام دارو را با نام بیمار و دستور پزشک مطابقت دهید1.
دستها را تمیز کنید2.
ترجیحا فراورده را در فضای مخصوص این کار آماده کنید3.
موارد زیر را چک کنید4.
تاریخ انقضا1.
سالم بودن ویال دارو2.
صحیح بودن نحوه نگهداری دارو3.
بروشور دارو را به دقت مطالعه کنید5.
Liposomal amphotericin
3- 6 mg/kgConventional amphotericin
0.3-1.5 mg/kg
دستورالعمل آماده سازی داروهای وریدی
:موارد زیر را کنترل کنید6.
دوز دارو، رقیق کننده، حامل و سرعت تزریق1.
(فرم تلفیق دارویی)حساسیتهای دارویی بیمار 2.
مطمئن شوید که نحوه مصرف دارو را به طور کامل متوجه شده اید3.
ا محاسبات لازم برای تعیین دوز و غلظت دارو را انجام دهید و آن را ب7.شخص دیگری چک کنید
حتما برای فراورده تهیه شده برچسب تهیه کنید8.
دستورالعمل آماده سازی داروهای وریدی
موارد زیر در بر چسب دارو باید ذکر شود
name of the medicine;
strength (dose);
route of administration;
diluent and final volume;
patient’s name;
date and time of preparation;
expiry date and time;
initials of the practitioner preparing the medicine
initials of second checker
میزان خطاها در تجویز داروهای وریدی
Errors in the administration of intravenous medications, BMJ quality & safety,
2011
میزان خطاها در تجویز داروهای وریدی
Errors in the administration of intravenous medications, BMJ quality & safety,
2011
Sodium Content
Some medicines, e.g. many antibiotics, are formulated with
a considerable sodium content; for example,
metronidazole contains 13.15mmol/500-mg bag.
This may be clinically significant and may need to taken
into account when therapeutic choices are made.
pH
help practitioners predict possible Y-site incompatibilities of medicines when no compatibility information exists
Injections with greatly differing pH values should not be administered concurrently down the same line as this may result in either precipitation or inactivation of the medicines
for example, the pH of phenytoin injection is 12 and the pH of haloperidol injection is 3, making them incompatible
The pH can also give the practitioner an indication of the irritancy of the drug.
Medicines that are either highly acidic or alkaline may be harmful if extravasation into the surrounding tissue occurs,causing tissue damage.
Light-sensitive infusions
Some drugs undergo photolysis and photodegradation if
exposed to natural daylight (ultraviolet radiation) and
fluorescent light during administration.
This can result in loss of therapeutic effect and the
production of toxic products.
Light-sensitive infusions
To reduce these reactions, the products must be
protected from light not only during storage but also once
diluted and ready for use.
Periodic visual inspection of the diluted solution for the
occurrence of discoloration and/or precipitation is
recommended during its infusion.
Visual inspection of prepared
product
All products prepared for intravenous use make reference
to this requirement as part of the preparation procedure.
Hold the syringe or infusion container up to a light
source and, while looking straight through the solution,
invert the product. Usually all that is seen are air bubbles
Observe for a few seconds for anything (particles) moving
downwards and any untoward color changes as described
in the specific monograph.
Displacement value
Injection products formulated as dry powders
or lyophilised cakes must be reconstituted
with a suitable diluent before administration.
Sometimes the final volume of the injection is
greater than the volume of liquid added to the
powder.
This volume difference is called the
displacement value
Displacement value
Example:
The displacement value of amoxicillin injection
250mg is 0.2 mL.
If 4.8mL of diluent is added to a 250-mg vial, the
resulting volume is 5mL, i.e. 250mg in 5 mL.
If 5mL of diluent is added, the resulting volume is
5.2 mL, i.e. 250mg in 5.2mLor 240.38mg in 5mL.
Displacement value
This must be taken into account when reconstituting the
drug if only part of the vial is to be used.
Cefotaxime:
Reconstitute each 500-mg vial with 2mL WFI (use 4mL for
each 1-g vial; 10mL for each 2-g vial)
Displacement value 0.2mL/500mg; 0.5mL/1 g; 1.2 mL/2 g
Flushing intravenous lines and
cannulas
Flushing between the administration of different
medicines
To avoid any problems with incompatibilities.
Ensures the total drug dose is presented for systemic effect
Prolongs the viability of the cannula or line
If two drugs being administered one after the other are
known to be compatible, then flushing the line or cannula
need only be done before and after administration of the
medicines.
Flushing intravenous lines and
cannulas
Commonly 5-10mL of NaCl 0.9% or Gluc 5% is used to
flush the dead space of a cannula, whereas 20mL is usually
needed for an administration set.
The practitioner must check each monograph before
deciding which flush to use, to ensure that both drugs are
compatible with the chosen flush.
Flushing intravenous lines and
cannulas
Frequent flushing of unused lines is also necessary in
order to maintain patency of the line or cannula.
Safe admixture
A safe admixture is one that is:
Free from microorganisms
Free from particulate matter ,undecomposed and clinically compatible
Incompatibility
Reaction between two or more drugs are be administration
through single IV line or given in a single solution are no
longer safe or effective for patients
Characteristics:
Color Change
Hazy Appearance
Precipitation
Not all Incompatibility are
dangerous
Some are just normal
Color Change:
Cefazolin or Dobutamin may show some color change but not a sign of
incompatibility
Hazy Appearance:
When Ceftazidime is reconstituted, CO2 gas is released and cause a Hazy
Appearance
Precipitation:
When Paclitaxel is refrigerated , dissolve again at room temperature
Contributing Factors
Light:
Amphotericin,Cisplatin,Metronidazole must be protected from light
Temperature:
Cefazolin is stable at room temperature for 24 hours but under
refrigeration for 14 days
Consentration dependent:
Co-trimoxazole 5 ml/ml D5W stable for 2 hours,where as 5ml/125 ml is
stable for 6 hours
Length of time in solution:
Meropenem is stable when diluated in NS at room temperature for≤ 4
hours and under refrigeration≤ 24 hours
Difference in pH
Types of Incompatibilities
Therapeutic Incompatibility
Physical Incompatibility
Chemical Incompatibility
Drug IV Container Incompatibility
Physical Incompatibility
The incompatibility that is mainly on solubility changes and
container interactions
Insolubility
Sorption Phenomena
Gas formation
Change of pH of solution
Prevention
i. Do not administer a precipitate forming drug
ii. Avoid mixing drugs prepared in special diluents with other drugs
iii. In administration of multiple intravenous medications, prepare each drug in a
separate syringe
Chemical Incompatibility
Results from the molecular changes or rearrangement and
leads to chemical decomposition
Hydrolysis
Oxidation reaction
Reduction reaction
Photolysis
Prevention
i. Store drugs in relatively water-proof containers
ii. Minimize the exposure time of the drug
iii. Keep away from suspected reducing agents
iv. Storing drugs in lightproof containers can usually prevent photolysis
Drug IV Container Incompatibility
Incompatibility that arise from the chemical reaction of the
drug and the Intravenous container
Adsorption:
The property of a solid/liquid to attract and hold to its surface a gas, liquid, solute
or suspension e.g: propofol
General Ways Of Prevention/ Minimization Of
Incompatibilities
Mix thoroughly when a drug is added to the preparation
Minimize the number of drugs mixed together in an IV solution
Separation of drug doses by time and place
Solutions should be administered promptly after mixing so that
occurrence potential reactions can be minimized
Usage of multi-lumen catheters
Use in-line filters
Always refer to compatibility references (Check for compatibility)
Checking IV Compatibility
Checking IV Compatibility
Checking IV Compatibility
Checking IV Compatibility
A multi-dose vial is a vial of liquid medication intended
for parenteral administration (injection or infusion) that
contains more than one dose of medication.
Multi-dose vials are labeled as such by the manufacturer
and typically contain an antimicrobial preservative to help
prevent the growth of bacteria.
The preservative has no effect on viruses and does not
protect against contamination when healthcare personnel
fail to follow safe injection practices.
Multi-dose vials should be dedicated to a single patient whenever possible.
multi-dose vials must be used for more than one patient, they should only be kept and accessed in a dedicated clean medication preparation area (e.g., nurses station), away from immediate patient treatment areas.
This is to prevent inadvertent contamination of the vial through direct or indirect contact with potentially contaminated surfaces or equipment that could then lead to infections in subsequent patients.
If a multi-dose vial enters an immediate patient treatment area, it should be dedicated for single-patient use only.
If a multi-dose has been opened or accessed (e.g., needle-
punctured) the vial should be dated and discarded within
28 days unless the manufacturer specifies a different
(shorter or longer) date for that opened vial.
If a multi-dose vial has not been opened or accessed (e.g.,
needle-punctured), it should be discarded according to
the manufacturer’s expiration date.
If using a multi-dose vial with a rubber stopper and a sharp safe needle system:
1. Remove the thin seal cap from the top of the vial without touching the rubber stopper.
2. Clean the rubber stopper with antiseptic.
3. Using the appropriate sharp safe needle for medication withdrawal and injection, inject a volume of air into the vial equivalent to the amount of solution to be withdrawn.
4. Insert the spike of the sharp safe needle into the vial until the “wing” of the pin touches the vial’s rubber stopper.
5. Hold the vial with the non-dominant hand and turn it up and pull the sharp safe needle back to where the bevel is beneath the fluid level.
If using an ampoule:
1. Lightly tap, shake or swirl the ampoule to dislodge any solution from the neck of the container.
2. Ensure the glass ampoule is appropriately wrap/covered for your protection i.e. by an ampoule cracker, antiseptic swab, gauze, etc.
3. Grasp the ampoule, snap off the top away from you and others, and discard the top in an appropriate sharps disposable container.
4. Insert the appropriate sized sharp safe needle into ampoule and draw up the appropriate amount of solution, and then remove the needle from the ampoule.
5. Do not allow the needle to touch edges of ampoule
6. Gently advance the plunger of the syringe to expel air from the solution.
Remove the filled syringe with the drawing up needle
attached. Do not leave the drawing up needle in the vial.
Avoid touching the top of the vial.
Detach the filled syringe and attach a new sterile injection
needle.
Hold the vial on a fat surface. Pierce the self-sealing
stopper in the center with the needle tip and inject the
measured air into the space above the solution. Do not
inject air into the solution. If the vial in use is a single-use
vial, there is no need to inject air into the vial.
Sterile for 96h
Not suitable for suspensions: NPH
A drug in powdered form is necessary when a medication is unstable as a liquid form for a long period
Flush IV line before and after administration. The most com m on fluid administered as an IV flush is sodium chloride 0.9%. In some instances, glucose 5% may be used if it is more suitable for use due to compatibility with the IV medicine being administered.
Insert the diluent syringe into the vial, via the rubber cap - at a 45 degs angle, with needle bevel uppermost. Changing the angle to 90 degs as the needle pushes through is considered to minimise coring, in which rubber is forced into the lumen of the needle with the resultant risk that it may then be injected into the patient (Dougherty and Lister, 2004);
INTRAMUSCULAR INJECTION SITES
Deltoid • Used for smaller volumes • Typically no more
than 1 mL • Some sources state 2 mLs can be given here,
but this is painful for the patient
Ventrogluteal and Dorsogluteal • Used for larger volumes
• Typically less than 3 mLs • Some resources state up to
5mLs but this is very painful for the patient •
Ventrogluteal • The safest site for adults and children
older than 7 months • Deep and not close to any major
blood vessels
Z TRACK METHOD
• Pulling the skin downwards or sideways at the site
before injection. Must remove needle from injection site
prior to releasing the skin because the needle could snap
off and remain in the muscle • After removing the needle
the track is closed when the skin is released, preventing
leakage of medication into the subQ tissue or even out of
the injection site itself • Can be utilized with all IM
injections but must be utilized with caustic medications
or medications that will stain the skin • Caustic –
Rocephin and Phenergan • Discoloration –Vit B12 and
Iron
There are two main reasons for diluting medicines within
neonatology and paediatrics. Firstly the dosages required
are usually very small. Sometimes the volume required is
so small that it is not straightforward to measure it
accurately. See BOX 6 for a worked example. Secondly
some drugs require further dilution for reasons such as
viscosity and/or irritation of veins, e.g., phenobarbitone
should be diluted by 10 times the volume of drug drawn
up